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WeightlessnessDI-CuffNCT03915457

Thigh Cuffs to Prevent the Deconditioning Induced by 5 Days of Dry Immersion

A study testing Thigh cuffs intervention in people with Weightlessness and Weightlessness; Adverse Effect, run by Centre National d'Etudes Spatiales at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objective of the study is to investigate whether thigh cuffs help to prevent and/or reduce the deconditioning induced by 5 days of dry immersion and in particular the fluid shift and its related ophthalmological disorders. Read more about this study

Who is it for?
Ages 20 to 45 years, men onlyHealthy volunteers can take part
What is being tested?
Thigh cuffs intervention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteFrance
Study dates
18 Nov 2018to 23 Mar 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit),
  • Age 20 to 45,
  • No overweight nor excessive thinness with BMI (weight Kg/ height m2) between 20 and 26,
  • Height between 158 and 185 cm,
  • No personal nor family past record of chronic or acute disease or psychological disturbances which could affect the physiological data and/or create a risk for the subject during the experiment,
  • Fitness level assessment:
Show all 16Show fewer
  • if age < 35 years: 35 ml/min/kg < VO2max < 60ml/min/kg
  • if age > 35 years: 30 ml/min/kg < VO2max < 60ml/min/kg
  • Walking between 7000 - 8000 steps/day,
  • Active and free from any orthopedic (in particular no vertebral fracture, scoliosis or herniated disc) musculoskeletal and cardiovascular disorders,
  • Non smokers,
  • No alcohol, no drug dependence and no medical treatment,
  • No antibiotic treatment in the 2 previous months before the beginning of the study,
  • Covered by a Social Security system,
  • Have signed the information consent,
  • Free of any engagement during the study.

Who cannot join

  • - Past record of orthostatic intolerance,
  • Cardiac rhythm disorders,
  • Chronic back pains,
  • Vertebral fracture, scoliosis or herniated disc,
  • Glaucoma,
  • HTA,
Show all 29Show fewer
  • History of migraines,
  • History of hiatus hernia or gastro-esophageal reflux,
  • History of thyroid dysfunction, renal stones, diabetes,
  • History of head trauma,
  • Past records of thrombophlebitis, family history of thrombosis or positive response in thrombosis screening procedure (anti thrombin III, S-protein, C-protein, factor V Leiden mutation and the mutation 20210 of the prothrombin gene),
  • Individuals exhibiting mutations involved in hereditary hemochromatosis (HAMP, HFE, HFE2, SCL40A1 and TRF2),
  • Abnormal result for lower limbs echo-doppler,
  • History or active claustrophobia,
  • History of genetic muscle and bone diseases of any kind,
  • Bone mineral density: T-score ≤ -1.5 on the hip,
  • Osteosynthesis material, presence of metallic implants or any other contra-indication for MRI,
  • Poor tolerance to blood sampling,
  • Having given blood (more than 8ml/kg) in a period of 8 weeks or less before the start of the experiment,
  • Antibiotic treatment in the 2 previous months before the beginning of the study,
  • Vegetarian or vegan,
  • History of food allergy,
  • Positive reaction to any of the following tests: HVA IgM (hepatitis A), HBs antigen (hepatitis B), anti-HVC antibodies (hepatitis C), anti-HIV1+2 antibodies,
  • Subject already participating or in the exclusion period of a clinical research,
  • Refusal to give permission to contact his general practitioner,
  • Incarcerated persons,
  • Subject who, in the judgment of the investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development,
  • Subject who has received more than 4500 Euros within 12 months for being a research subject.
  • Subject under guardianship or trusteeship.

Trial locations and contacts

1 site in 1 country.

France1 site
  • Medes-Imps

    Toulouse, 31400

Other trials in France

About this study

Official title: Effects of Thigh Cuffs to Prevent the Deconditioning Induced by 5 Days of Dry Immersion Used as a Ground-based Model to Study the Effects of Weightlessness

The objective of the study is to investigate whether thigh cuffs help to prevent and/or reduce the deconditioning induced by 5 days of dry immersion and in particular the fluid shift and its related ophthalmological disorders. During a randomized 5 day dry-immersion study in 20 healthy male adults the two following aims will be undertaken:

  • Ten scientific protocols will assess the changes in the cerebral, ocular, cardiovascular, metabolism, cognitive, muscle and bone systems.
  • In the above mentioned systems, the potential beneficial effects of the countermeasure protocol will also be investigated.
Read the detailed description

Space flights have shown the possibilities and limitations of human adaptation to space. For the last 50 years, results showed that the space environment and microgravity in particular, cause changes that may affect the performance of astronauts. These physiological changes are now better known: prolonged exposure to a weightlessness environment can lead to significant loss of bone, muscle mass, strength, cardiovascular and sensory-motor deconditioning, immune, hormonal and metabolism changes. Nevertheless, more recent missions have revealed a new suite of physiological adaptations and consequences of space flight. Indeed, astronauts exposed to prolonged weightlessness experience hyperopic shifts and structural alteration in the eye (e.g., choroidal folds and optic disc edema). This condition was defined by NASA as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Some of these vision changes remain unresolved for years after flight. This phenomenon has most likely existed since the beginning of human space flight, but is just recently being recognized as a major consequence of adaptation to microgravity. Changes in vision and eye structure are thought to be the result of prolonged exposure to space flight-induced headward fluid shifts and elevated intracranial pressure. Loss of the hydrostatic pressure gradient during spaceflight leads to this redistribution of body fluids toward the head. To prepare for future manned missions beyond the low Earth Orbit, the mechanisms underlying SANS syndrome have to be investigated and countermeasures designed to reverse or prevent SANS are required. Venoconstrictive thigh cuffs (VTCs) represent one possible countermeasure to mitigate a headward fluid shift. The Russian Space Agency uses VTCs (bracelets) to sequester fluid in the lower limbs and mitigate the subjective sensation of head congestion during space-flight. Moreover, experiments on 6-month Mir missions demonstrated that bracelets reduced jugular vein cross-sectional area in cosmonauts by 12% to 20%. However, it is unknown how VTCs (including bracelets) affect ocular physiologic features. The space agencies are actively engaged in studying the initiation and progression of SANS syndrome through studies on the International Space Station and on the ground. Indeed, considering the limited number of flight opportunities, the difficulties related to the performance of in-flight experiments (operational constraints for astronauts, limited capabilities of in-flight biomedical devices), ground-based experiments simulating the effects of weightlessness are used to better understand the mechanisms of physiological adaptation, design and validate the countermeasures. Different methods are used to simulate microgravity on Earth. However, two separate approaches, -6° head-down bed rest (HDBR) and dry immersion (DI) have provided possibilities for long-term exposures with findings closest to those seen with a weightless state. They produce changes in body composition (including body fluid redistribution), cardiovascular and skeletal muscle characteristics that resemble the effects of microgravity. The common physiological denominator is the combination of a cephalad shift of body fluids and reduced physical activity. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body. Dry immersion means immersing into the thermoneutral water covered with special elastic free floating waterproof fabric. The subject, surrounded by film and "free suspended" in the water mass, remains dry. During horizontal immersion, pressure forces are distributed nearly equally around the entire surface of the body (only the head and neck are not entirely supported by water). The absence of mechanical support of specific zones during immersion creates a state akin to weightlessness that is called "supportlessness". Physiological changes under DI develop more rapidly and are more profound than under HDBR. This advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.

The present study is organized in this context by the French space agency (CNES) to assess on twenty healthy male volunteers the effects of thigh cuffs to prevent the deconditioning induced by 5 days of dry immersion and in particular the fluid shift and its related ophthalmological disorders. Using an integrated approach, the CNES has selected ten scientific protocols to assess the changes in the different physiological fields and the potential beneficial effects of the countermeasure to prevent and/or reduce these changes.

Being tested
Dry immersion Control Group, Thigh cuffs intervention
Keywords
Simulated Microgravity, Weightlessness, Countermeasure, Dry immersion, Supportlessness

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dry immersion Control GroupOther

    Subjects are immersed up to the neck for 5 days in a specially designed bath filled with tap water.

  • Thigh cuffs interventionOther

    Subjects are immersed up to the neck for 5 days in a specially designed bath filled with tap water. During the 5 days of dry immersion, the subjects will wear the thigh cuffs daily for 10 hours during the day (8 am to 6 pm). Thigh cuffs are strips of fabric with inserts of elastic fabric. Different sizes exist to adapt to different thighs. Each cuff has five tightening positions (from 1 to 5) and they will be tightened at the upper third of the thighs to create an occlusion pressure of about 30 mmHg.

Study groups in NCT03915457
Study groupRoleWhat they receive
Dry immersion Control GroupExperimental5 days of dry-immersion
Receives: Other: Dry immersion Control Group
Thigh Cuffs interventionExperimental5 days of dry-immersion with thigh cuffs
Receives: Other: Thigh cuffs intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation

    The optic nerve sheath diameter (ONSD) variations will be measured by echography.

    Measured: Baseline and five days of dry-immersion

Secondary outcomes (15)
  1. Change in the optic nerve fibers thickness

    Thickness of the optic nerve fibers will be measured by Optical Coherence Tomography (OCT)

    Measured: Baseline and five days of dry-immersion

  2. Change in cerebral structures and in venous circulation of the brain by MRI

    Visualization of cerebral structures and intracranial venous system will be performed by MRI coupled with injection of gadolinium

    Measured: Baseline and five days of dry-immersion

  3. Change in cerebral perfusion

    Cerebral perfusion will be assessed by HMPAO scintigraphy

    Measured: Baseline and five days of dry-immersion

  4. Change in intraocular pressure.

    Intra ocular pressure (IOP) will be measured by applanation tonometry

    Measured: Baseline and five days of dry-immersion

  5. Change in orthostatic tolerance

    Orthostatic tolerance will be assessed during a Lower Body Negative Pressure test (LBNP test)

    Measured: Baseline and five days of dry-immersion

  6. Change in body fluid compartments by bioelectrical impedance analysis

    Extracellular, intracellular and total body water will be estimated by bioimpedance

    Measured: Baseline and during five days of dry-immersion

  7. Change in circadian rhythms of blood pressure

    Continuous 24-h recording of blood pressure will be performed by SOMNOtouch™ NIBP system designed for ambulatory continuous measurements

    Measured: Baseline and during the five days of the dry-immersion period

  8. Measurement of the fluid shift towards the cephalic region by ultrasound

    The hemodynamic and morphologic consequences of the fluid shift on the cephalic organs (thyroid, eyes), cephalic blood vessels (jugular vein, carotid, femoral, middle cerebral vein) will be investigated by ultrasound

    Measured: The first day to quantify the short term effect and the fourth day of dry-immersion to quantify the long term effect of fluid shift

  9. Change of whole-body and skeletal muscle metabolic flexibility (i.e. capacity to adapt fuel oxidation to fuel availability)

    Whole-body metabolic flexibility will be measured through the changes in respiratory quotient (RQ) from fasting state to postprandial state induced by high-carbohydrate standard meal, Skeletal muscle metabolic flexibility will be assessed in primary cell culture (cell isolation from biopsies of the vastus lateralis muscle).

    Measured: Baseline and 4 days of dry-immersion

  10. Change in expression pattern of atrophic and phenotypic modifiers in skeletal muscle

    Vastus Lateralis needle biopsies will be performed before and at the end of the 5 days of dry-immersion. The expression pattern of many proteins implied in the regulation of skeletal muscle homeostasis will be studied using biochemical technics.The contractile proteome will be investigated by analyzing the phenotype expression of myosin isoforms (heavy-MHC and light-MLC chains), regulatory proteins, i.e. troponin (TnI,TnC and TnT) and tropomyosin isoforms, main proteins implied in the sarcoplasmic reticulum function i.e. Ca-ATPase SERCA and Ca leakage channel RyR (primary antibodies from Sigma, Cell Signalling, Millipore).

    Measured: Baseline and 5 days of dry-immersion

  11. Change in muscle transcriptome profile

    Vastus Lateralis needle biopsies will be performed before and at the end of the 5 days of dry-immersion. The muscle gene expression will be analyzed by microarray technology

    Measured: Baseline and 5 days of dry-immersion

  12. Measurement of muscle contractile properties using skinned fibers

    Vastus Lateralis needle biopsies will be performed before and at the end of the 5 days of dry-immersion. Skinned fibers will be prepared by processing in skinning solution. Maximal tension and calcium affinity of single skinned fibers will be assessed using tensiometry.

    Measured: Baseline and 5 days of dry-immersion

  13. Measurement of fat cell invasion into skeletal muscle

    Vastus Lateralis needle biopsies will be performed before and at the end of the 5 days of dry-immersion. The expression of markers related to adipocytes structure and function (PPAR-γ, CEBP-α,CEBP-δ, lipoprotein lipase, ACLP, adipsin, leptin, adiponectin, FABP4, UCP1, IL6, IL15, CD36, GLUT4)will be quantified by RT-qPCR and western blotting. Additionally, the CD34+CD15+CD56- specific adipogenic progenitors of skeletal muscle will be quantified by RT-qPCR and western blotting.

    Measured: Baseline and 5 days of dry-immersion

  14. Change in the balance of bone remodeling markers

    Concentration of bone formation markers [bone-specific Alkaline Phosphatase (bAP), procollagen type I N-terminal propeptide (P1NP), total osteocalcin, uncarboxylated and carboxylated osteocalcin] and of bone resorption markers [C-terminal cross-linked telopeptide of type I collagen (CTx)] will be analyzed by automated chemiluminescence immunoassay or by enzyme-immunoassay kits.

    Measured: Baseline, during and after 5 days of dry-immersion

  15. Change in the composition of the intervertebral disc (IVD).

    The concentration of glycosaminoglycan (GAG) and water in the IVD will be measured by MRI with spectroscopy (MRS)

    Measured: Baseline and 5 days of dry-immersion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2019
  2. Study start18 Nov 2018
  3. Primary completion22 Mar 2019
  4. Study completion23 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
A monocentric open parallel randomized and controlled study.
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03915457
Sponsor's protocol ID
18-179
Acronym
DI-Cuff
Status last verified
Apr 2019
First submitted
5 Mar 2019
Last updated
21 Aug 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Arbeille P, Herault S, Fomina G, Roumy J, Alferova I, Gharib C. Influences of thigh cuffs on the cardiovascular system during 7-day head-down bed rest. J Appl Physiol (1985). 1999 Dec;87(6):2168-76. doi: 10.1152/jappl.1999.87.6.2168.

    PubMed 10601164
  • Balasubramanian S, Tepelus T, Stenger MB, Lee SMC, Laurie SS, Liu JHK, Feiveson AH, Sadda SR, Huang AS, Macias BR. Thigh Cuffs as a Countermeasure for Ocular Changes in Simulated Weightlessness. Ophthalmology. 2018 Mar;125(3):459-460. doi: 10.1016/j.ophtha.2017.10.023. Epub 2017 Nov 16. No abstract available.

    PubMed 29153458
  • De Abreu S, Amirova L, Murphy R, Wallace R, Twomey L, Gauquelin-Koch G, Raverot V, Larcher F, Custaud MA, Navasiolava N. Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise. Front Physiol. 2017 Oct 13;8:799. doi: 10.3389/fphys.2017.00799. eCollection 2017.

    PubMed 29081752
  • Kermorgant M, Leca F, Nasr N, Custaud MA, Geeraerts T, Czosnyka M, Arvanitis DN, Senard JM, Pavy-Le Traon A. Impacts of Simulated Weightlessness by Dry Immersion on Optic Nerve Sheath Diameter and Cerebral Autoregulation. Front Physiol. 2017 Oct 12;8:780. doi: 10.3389/fphys.2017.00780. eCollection 2017.

    PubMed 29075198
  • Navasiolava NM, Custaud MA, Tomilovskaya ES, Larina IM, Mano T, Gauquelin-Koch G, Gharib C, Kozlovskaya IB. Long-term dry immersion: review and prospects. Eur J Appl Physiol. 2011 Jul;111(7):1235-60. doi: 10.1007/s00421-010-1750-x. Epub 2010 Dec 14.

    PubMed 21161267

Questions about this trial

What is this clinical trial studying?

A study testing Thigh cuffs intervention in people with Weightlessness and Weightlessness; Adverse Effect, run by Centre National d'Etudes Spatiales at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in optic nerve sheath diameter (ONSD) considered as an indirect marker for intracranial pressure (ICP) estimation (time frame: Baseline and five days of dry-immersion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03915457, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2019.

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